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Acute intravenous injection and short‐term oral administration of N G ‐nitro‐ l ‐arginine methyl ester to the rat provoke increased pressor responses to agonists and hypertension, but not inhibition of acetylcholine‐induced hypotensive responses
Author(s) -
López Ruth M.,
Pérez Teresa,
Castillo Carlos,
Castillo María C.,
Castillo Enrique F.
Publication year - 2011
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2010.00852.x
Subject(s) - phenylephrine , angiotensin ii , medicine , vasodilation , vasoconstriction , endocrinology , agonist , nitric oxide , blood pressure , acetylcholine , renin–angiotensin system , receptor
In experiments in vivo, we studied whether the endothelial dysfunction induced by nitric oxide (NO) synthesis inhibition is simultaneously or sequentially manifested as a reduced level of endothelium‐dependent agonist‐induced vasodilatation, an increased responsiveness to vasoconstrictors, and hypertension. Vascular responses to acetylcholine, phenylephrine, and angiotensin II were measured in pithed rats after acute intravenous injection (100 mg/kg) and short‐term oral administration of N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME; 60 mg/kg per day) for 1 and 3 days ( l ‐NAME 1d and l ‐NAME 3d , respectively). Pithed rats were chosen because drug‐induced cardiovascular responses reflect only peripheral effects. Parallel experiments examined mean arterial pressure (MAP) values in anesthetized rats. After short‐term l ‐NAME 1d and l ‐NAME 3d treatments, the MAP was significantly elevated in anesthetized but not pithed rats. Acute intravenous administration of l ‐NAME elevated MAP in pithed rats. Intravenous infusion of phenylephrine was used to compensate for the pressor response induced by l ‐NAME in pithed animals. The maximum decrease and duration of the hypotensive responses to acetylcholine were unaltered by the acute and both short‐term l ‐NAME treatments in pithed rats. These treatments, on the other hand, increased phenylephrine‐ and angiotensin II‐induced pressor responses in pithed animals. In isolated aortic rings prepared from pithed rats treated acutely and short‐term with l ‐NAME, acetylcholine‐induced relaxations were inhibited. Thus, the inhibition of NO‐dependent vasodilator tone after acute intravenous injection and short‐term oral l ‐NAME administration may be associated with vascular smooth muscle hyper‐responsiveness to pressor agonists and hypertension, whereas the hypotensive responses to acetylcholine could not be associated with the l ‐NAME‐induced endothelial dysfunction in pithed rats.